The polyphenol group rutin (R) appears to influence isotype expression, because R-BSA conjugates induce anti-BSA responses in mice that show a significant decrease in hemagglutinating antibodies (HA) to BSA, as compared to mice immunized with BSA. However, the level of IgE antibodies to BSA is unaltered. To determine if suppressor cells for isotypes other than IgE are induced by R-BSA, cell transfers were performed. The results were consistent with the view that the decrease in HA titer to BSA in R-BSA immunized mice is not due to the activation of suppressor cells for isotypes other than IgE. Inasmuch as the IgE response in mice is associated with the production of IL-4 by Th2 cells, we analyzed the factors produced by spleen cells cultured with R-BSA. We found that supernatant from spleen cells cultured with R-BSA contained IL-4 as determined by the enhanced expression of Fc epsilon R (CD23) on B cells. This enhancement was inhibited by 11B11, the anti-IL-4 mAb. IL-2, a product of Th1 cells, was not detected in these supernatants. Moreover, IL-4 mRNA, but not IL-2 mRNA, was detected by Northern blot analysis of RNA from spleen cells cultured with R-BSA. Taken together the data suggest that the polyphenol containing compounds preferentially activate Th2 cells, thereby favoring IgE production.